کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6263364 1613871 2014 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research ReportEffects of dexmedetomidine on P2X4Rs, p38-MAPK and BDNF in spinal microglia in rats with spared nerve injury
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Research ReportEffects of dexmedetomidine on P2X4Rs, p38-MAPK and BDNF in spinal microglia in rats with spared nerve injury
چکیده انگلیسی


- P2X4R receptors which are mainly expressed in microglia play an important role in SNI rats.
- Dexmedetomidine can attenuate hyperalgesia of SNI rats.
- Dexmedetomidine can inhibit the activity of microglia.
- Analgesic mechanism of dexmedetomidine may affect P2X4R/p38-MAPK/BDNF.

Microglia in the spinal cord is evidenced to play a crucial role in neuropathic pain. Spinal P2X4 receptors (P2X4Rs), which are mainly expressed in microglia, have been investigated for their roles in neuropathic pain. Dexmedetomidine (DEX), a highly selective agonist of α2-adrenergic receptors, is clinically applied to sedation and analgesia. Despite the proposed mechanisms underlying DEX-induced analgesia, the possible interactions between DEX and P2X4Rs at a molecular level have not been elucidated. We designated the spared nerve injury (SNI) to establish the neuropathic pain model. Mechanical paw withdrawal threshold (MWT) was measured to evaluate the sensitivity of neuropathic pain in rats. MWT was significantly decreased in SNI rats versus control rats. Expressions of spinal P2X4Rs, phosphorylated p38-mitogen-activated protein kinase (p-p38-MAPK) and brain-derived neurotrophic factor (BDNF) were upregulated in SNI rats. Immunofluorescence assay indicated higher densities of microglia and P2X4Rs, which appeared yellow in colour, suggesting they were co-labelled. Intraperitoneal injections of DEX 40 μg/kg for 14 consecutive days markedly reversed the SNI-induced decline of MWT; the activation of microglia was markedly inhibited; in addition, the protein expressions of P2X4Rs, p-p38-MAPK and BDNF were significantly downregulated. Thus, DEX could attenuate the neuropathic pain in SNI rats, of which the mechanism might be related to the down-expressed P2X4Rs, p-p38 and BDNF in microglia of spinal dorsal horn.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1568, 3 June 2014, Pages 21-30
نویسندگان
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